MRI is a non invasive technique with broad diagnostic value. The technique has gained wide clinical acceptance and is of great importance in diagnostic medicine. However, despite significant technological advancements (increasing field strength and cooling of electronics), applications of MRI are limited by an intrinsically low sensitivity.
Some alternatives to enhance its sensitivity have been developed which involve ex vivo nuclear spin polarization of agents, prior to administration and consequent in vivo MR signal measurement.
EP 1544634 discloses some of said alternative techniques, comprising among others, Dynamic Nuclear Polarisation (DNP), Para Hydrogen Induced (PHI) polarisation and Polarisation Transfer from a hyperpolarised noble gas.
In particular, U.S. Pat. No. 6,466,814 describes a method of magnetic resonance investigation comprising the production of a hyperpolarised solution of a proper high T1 agent selected from a series of possible candidates, followed by the administration of said solution to a subject.
During hyperpolarisation of a sample (particularly as regards the DNP methods), very low temperature are often required in order to have the sample polarised in a proper solid form. In this respect, it is known in the art (see e.g. US2008095713) that successful polarization levels are generally achieved by DNP technique when the mixture upon freezing forms a glass rather than a crystallized sample.
The applicant noticed that while many molecules (e.g. carboxylic acids) are not capable of forming a glass in their pure form as such, thus requiring the addition of a glass-forming agent thereto, some precursors thereof (e.g. anhydrides or esters) are instead capable of forming a neat glass substantially without the need of any glass-forming additive.
Furthermore, other substrates may have stability problems, so that they are easily and quickly degraded into non active substances or non desired compounds. For instance, some active substrates can be transformed, at least in part, into their respective non-active isomers.
Hence, according to the invention, the use of a stable DNP hyperpolarised precursor which can readily be transformed into the desired hyperpolarized substrate upon dissolution in an aqueous carrier (e.g. an anhydride or an ester precursor of a carboxylic acid), is particularly advantageous. Applicant has further observed that certain final substrates may be obtained with a higher degree of polarization if the DNP polarisation is effected on their respective precursors (e.g. an ester) rather than on the molecule of the substrate itself (e.g. the respective carboxylic acid).
Hence, according to the invention, the use of a stable precursor which can readily be transformed into the desired hyperpolarized substrate upon dissolution in an aqueous carrier, such as an anhydride or an ester precursor of a carboxylic acid, is particularly conveniently.
Advantageously, suitably selected precursors may be used to prepare two or more different hyperpolarized substrates there from, or a mixture of a hyperpolarized substrate with a hyperpolarized MR contrast agent or a hyperpolarized pH reporter.
For these and other advantages which may be better appreciated by the skilled person upon reading the detailed description of the invention, the present invention provides a substantial innovative contribution over the state of the art.